LOCAL ANAESTHETIC TOXICITY
Higher Risk
Bupivacaine
Cocaine
Lower Risk
Prilocaine
NB Contraindicated < 6 months age (from product info “may affect
amount of oxygen in their blood)
Doses:
1% is 1 g/100 mL
Move decimal place to right (mg/ml)
Ie 0.5% Prilocaine = 5mg/ml
Adrenaline
1:1000 means 1 mg per 1 mL (ie, 0.1%)
Amides
Duration
Doses
Lignocaine (Xylocaine)
Medium (30-60
min)
Without epinephrine: 4.5 mg/kg; not to exceed 300
mg
Lignocaine with
epinephrine
Long (120-360
min)
With epinephrine: 7 mg/kg
Bupivacaine (Marcaine)
Long (120-240
min)
Without epinephrine: 2.5 mg/kg; not to exceed 175
mg total dose
Bupivacaine with
epinephrine
Long (180-420
min)
With epinephrine: 3mg/kg Not to exceed 225 mg
total dose
Prilocaine (Citanest)
Medium (30-90
min)
Body weight <70 kg: 8 mg/kg; not to exceed 500
mg
Body weight >70 kg: 600 mg
OR: Biers: 3mg/kg, Plain 6mg/kg, +Adr 8mg/kg
Comes in 0.5% = 250mg/50ml
= 5mg/ml (hence “0.5ml/kg of 0.5%” for biers =
2.5mg/kg
Ropivacaine (Naropin)
Long (120-360
min)
5 mg/kg; not to exceed 200 mg for minor nerve
block
Reduced dosage is indicated in
Debilitated or acutely ill
Very young children
Geriatric
Liver disease
Arteriosclerosis/Occlusive arterial disease
NB:
Topical doses can cause systemic toxicity, increased risk with abraded skin
Cocaine containing preps have been assoc with seizures in kids
Oral viscous lignocaine can cause toxicity with repeated doses
Central nervous system signs
Initial symptoms
Lightheadedness
Dizziness
Blurred vision
Tinnitus
Disorientation/Drowsiness
Higher-dose symptoms
Initial CNS excitation followed by a rapid CNS depression
Muscle twitching
Convulsions
Unconsciousness
Coma
Respiratory depression and arrest
Cardiovascular depression and collapse
Cardiovascular signs
Direct cardiac effects
Myocardial depression (tetracaine, etidocaine, bupivacaine),
Cardiac dysrhythmias (bupivacaine)
Several anesthetics also have negative inotropic effects on cardiac muscle that lead to
hypotension. Bupivacaine is especially cardiotoxic.
Peripheral effects
Vasoconstriction at low doses
Vasodilatation at higher doses (hypotension)
The range of signs and symptoms of cardiovascular toxicity may include:
Chest pain
Shortness of breath
Palpitations
Lightheadedness
Diaphoresis
Hypotension
Syncope
Hematological signs
Methemoglobinemia has been frequently reported in association with benzocaine use;
however, lidocaine and prilocaine have also been implicated. O-toluidine, the liver
metabolite of prilocaine, is a potent oxidizer of hemoglobin to methemoglobin.
Low levels (1-3%), methemoglobinemia can be asymptomatic
Higher levels (10-40%) may be accompanied by any of the following complaints:
Cyanosis
Cutaneous discoloration (gray)
Tachypnea
Dyspnea
Exercise intolerance
Fatigue
Dizziness and syncope
Weakness
ALLERGY
Amides are PABA derivatives  associated with allergy
Esters – no PABA but may contain preservative – methylparaben  allergy
Lignocaine allergy usually due to preservative
Preservative-free ligocaine can be obtained
Peripheral Neurotoxicity
Persistent numbness  from high doses
Low pH and sodium bisulfite in the mixture can be partially responsible for these
changes. Reversible skeletal muscle damage has also been reported
TREATMENT OF TOXICITY
1) Allergy/anaphylaxis: usual treatment
2) Resuscitation& Stabilization of potential life threats.
Ie Impending airway compromise, significant hypotension, and treatment of
dysrhythmias and seizures.
3) CNS complications/toxicity = controversial
No single remedy exists.
Seizures:
Benzodiazepines and barbiturates (eg, phenobarbital).
Avoid phenytoin (shares pharmacologic properties ie, Na+ channel blockade with
lidocaine  may potentiate toxicity.
4) Cardiovascular:
Prolonged PR, QRS, and QT intervals potentiating reentrant tachycardias with
aberrant conduction may herald cardiovascular toxicity.
Expect that cardiac resuscitation may be difficult and prolonged (30-45 min) Some
anaesthetics = very lipid soluble  require long time for redistribution. Most cases of
lignocaine-induced cardiac toxicity can be successfully treated with properly CPR due
to relatively short duration of action
Avoid class IB antidysrhythmic agents (may worsen toxicity)
Eg phenytoin, mexiletine (Mexitil), and tocainide (Tonocard)
Bupivacaine depresses conduction and contractility at low doses.
Lidocaine has been used successfully in bupivacaine-induced dysrhythmias, but its
additive CNS toxicity is still a major concern.
Even though bretylium theoretically should not potentiate CNS toxicity (as does
lidocaine), its benefits in cardiovascular resuscitation are unclear.
Evidence for use of amiodarone is also lacking
Potential Options in prolonged/refractory resuscitation
Adrenaline
Vasopressin
Cardiac pacing
Bypass/ECMO
Glucose/Insulin
Lipid Emulsion Infusion (in Bupivicaine toxicity)
Lipid Emulsion Infusion:
Lipid infusion accelerates the decline in bupivacaine myocardial content (reduced
tissue binding) by creating a lipid phase that extracts the lipid-soluble bupivacaine
molecules from the aqueous plasma phase. A beneficial energetic-metabolic effect
may also occur. To date, 3 successful case reports have been documented in humans.
Weinberg's recommended dosing regimen for use in humans
In cardiac arrest secondary to local anesthetic toxicity that is unresponsive to standard
therapy, intravenous administration of a lipid such as Intralipid 20% is recommended
in the following regimen:
1. Administer 1 mL/kg over 1 minute.
2. Repeat twice more at 3– to 5-minute intervals.
3. Then (or sooner if stability is restored), convert to an infusion at a rate of 0.25
mL/kg/min, continuing until hemodynamic stability is restored.
4. Increasing the dose beyond 8 mL/kg is unlikely to be useful.
5. In practice, resuscitate an adult weighing 70 kg as follows:
6.
a. Use a 500-mL bag of fat emulsion (Intralipid 20%) and a 50-mL
syringe.
b. Draw up 50 mL and give it stat intravenously, and then draw up and
give another 20 mL.
c. Do exactly the same thing up to twice more as the epinephrine is
given—if necessary or appropriate.
d. Then, attach the fat emulsion bag to a giving set and administer it
intravenously over the next 15 minutes.
Note that propofol (Diprivan) is not a component of lipid rescue. It is formulated in a
10% lipid emulsion and therefore an overdose of propofol (gram quantities) would be
necessary to provide an adequate dose of lipid emulsion. Propofol is contraindicated
when there is any evidence of cardiovascular toxicity.
Local Toxicity/nerve damage
Local ischemic or nerve toxicities may occur, particularly in the extremities with
prolonged anesthesia or epinephrine use. Suspected nerve damage should prompt
neurologic consultation for urgent peripheral nerve studies.
Vascular compromise
Eg limb ischemia: consult a vascular surgeon immediately.
Therapy for extravasation (eg, warm compresses, phentolamine, nitroglycerin cream)
should be initiated for localized vascular toxicity.
Methemoglobinemia
Initially treat symptomatically and then guided by blood levels of methemoglobin.
Methylene blue and hyperbaric oxygen may be required in severe cases.
Finally, the prevention of local anesthetic toxicity should always be the primary
consideration. Although all adverse reactions cannot be anticipated, complications can
be avoided by strict adherence to the guidelines of anesthetic dosing, identification
of patients at increased risk, and implementation of appropriate anesthetic application
techniques to avoid unintentional intravascular injection.